DNA stuck in the gears of the RNA production machine

Researchers have worked out the mechanism of transcription pausing in some bacteria by determining the structures of RNA polymerase in a complex with a DNA template, an RNA product, and a protein factor using cryo-electron microscopy (cryo-EM). The nucleotide addition cycle of bacterial RNA polymerase (RNAP) is depicted by cartoon models of template DNA (tDNA, green), RNA (red), trigger loop (TL, magenta), bridge helix (BH, blue), incoming NTP (red) and Mg2+ (yellow spheres) together with the conformational changes of RNAP (swiveling, folding Trigger loop) associated with each step of the nucleotide addition cycle. NusG and non-template DNA (ntDNA, light green) interaction (center panel) inhibits the RNAP swiveling, the Trigger loop folding allosterically thus pauses RNA synthesis.
Illustration Credit: Murakami Laboratory / Pennsylvania State University

Precise control of gene expression — ensuring that cells make the correct components in the right amount and at the right time — is vital for all organisms to function properly. Cells must regulate how genes encoded in the sequence of DNA are made into RNA molecules that can carry out cellular functions on their own or be further processed into proteins. One way gene expression is regulated is by pausing “transcription” — the process by which RNA is synthesized from its DNA template by an enzyme called RNA polymerase. Now, researchers have worked out the mechanism of transcription pausing in some bacteria using cryo-electron microscopy (cryo-EM), which allows them to determine to atomic scale the structures of the RNA polymerase before, during, and just after a pause of RNA production. Elucidating the mechanism of pausing transcription is crucial to understanding basic cellular function.

One of the key components of transcription pausing in the bacteria is a protein factor called NusG, which is conserved across organisms, including humans, such that the pausing mechanism revealed by this study may be broadly applicable for understanding gene regulation in all organisms on Earth. The insight could also be used to identify new anti-bacterial agents that target and inhibit transcription pausing thus disrupting proper gene expression and cellular function.

Creating 3D objects with sound

The use of sound waves to create a pressure field to print particles. 
Image Credit: © MPI for Medical Research, Heidelberg University/ Kai Melde

Creating 3D objects with sound

Scientists from the Max Planck Institute for Medical Research and the Heidelberg University have created a new technology to assemble matter in 3D. Their concept uses multiple acoustic holograms to generate pressure fields with which solid particles, gel beads and even biological cells can be printed. These results pave the way for novel 3D cell culture techniques with applications in biomedical engineering.

Additive manufacturing or 3D printing enables the fabrication of complex parts from functional or biological materials. Conventional 3D printing can be a slow process, where objects are constructed one line or one layer at a time. Researchers in Heidelberg and Tübingen now demonstrate how to form a 3D object from smaller building blocks in just a single step. “We were able to assemble microparticles into a three-dimensional object within a single shot using shaped ultrasound”, says Kai Melde, postdoc in the group and first author of the study. “This can be very useful for bioprinting. The cells used there are particularly sensitive to the environment during the process”, adds Peer Fischer, Professor at Heidelberg University.

Yellow evolution: Unique genes led to new species of monkeyflower

 Plants of the genus Mimulus (Monkeyflowers) have a great diversity of flower color and shape.
Photo Credit: Yuan Mimulus Lab, Pete Morenus | UConn

Monkeyflowers glow in a rich assortment of colors, from yellow to pink to deep red-orange. But about 5 million years ago, some of them lost their yellow. In the Feb. 10 issue of Science, UConn botanists explain what happened genetically to jettison the yellow pigment, and the implications for the evolution of species.

Monkeyflowers are famous for growing in harsh, mineral-rich soils where other plants can’t. They are also famously diverse in shape and color. And monkeyflowers provide a textbook example of how a single-gene change can make a new species. In this case, a monkeyflower species lost the yellow pigments in the petals but gained pink about 5 million years ago, attracting bees for pollination. Later, a descendent species accumulated mutations in a gene called YUP that recovered the yellow pigments and led to production of red flowers. The species stopped attracting bees. Instead, hummingbirds pollinated it, isolating the red flowers genetically and creating a new species.

UConn botanist Yaowu Yuan and postdoctoral researcher Mei Liang (currently a professor at South China Agricultural University), with collaborators from four other institutes, have now shown exactly which gene it is that changed to prevent monkeyflowers from making yellow. Their research, published this week in Science, adds weight to a theory that new genes create phenotypic diversity and even new species.

Mosquito’s DNA could provide clues on gene expression, regulation

Vinícius Contessoto (left) and José Onuchic are lead co-authors on the study published last month in Nature Communications.
Vinícius Contessoto
 is a researcher in the Center for Biological Theoretical Physics at Rice University.
José Onuchic
 is the Harry C. and Olga K. Wiess Chair of Physics and professor of chemistry and biosciences at Rice University.
Photo Credit: Gustavo Raskosky/Rice University

When it comes to DNA, one pesky mosquito turns out to be a rebel among species.

Researchers at Rice University’s Center for Theoretical Biological Physics (CTBP) are among the pioneers of a new approach to studying DNA. Instead of focusing on chromosomes as linear sequences of genetic code, they’re looking for clues on how their folded 3D shapes might determine gene expression and regulation.

For most living things, their threadlike chromosomes fold to fit inside the nuclei of cells in one of two ways. But the chromosomes of the Aedes aegypti mosquito — which is responsible for the transmission of tropical diseases such as dengue, chikungunya, zika, mayaro and yellow fever — defy this dichotomy, taking researchers at the CTBP by surprise.

The Aedes aegypti’s chromosomes organize as fluid-yet-oriented “liquid crystals,” different from all other species, according to their study published in Nature Communications.

How protein-rich droplets form

Martina Havenith-Newen has gained new insights by combining two methods.
Photo Credit: © RUB, Marquard

Terahertz spectroscopy can be used to explain the spontaneous formation of protein-rich droplets, which may lead to neurodegenerative diseases.

With the help of a new method, terahertz calometry, it is a research team of the Bochum Cluster of Excellence Ruhr Explores Solvation RESOLV succeeded in re-examining the spontaneous phase separation into a protein-rich and a low-protein phase in one solution. It is believed that the protein-rich droplets favor the formation of neurotoxic protein aggregates - a starting point for neurodegenerative diseases. The researchers around Prof. Dr. Martina Havenith, holder of the Chair for Physical Chemistry II at the Ruhr University Bochum, reports in the Journal of Physical Chemistry Letters from 6. February 2023.

Molecular level and time resolution in the picosecond range

The study is based on the work in the Terahertz-Calorimetry project, which was funded by the European Research Council with an Advanced Grant. "The visionary idea in the project was to marry two powerful techniques in physical chemistry - laser spectroscopy and calorimetry -" explains Grantee Martina Havenith.

Chemists Optimized Ceramic Material for Hydrogen Energy

The Institute of Hydrogen Energy is creating materials and technologies.
Photo Credit: Anna Popova

The team of scientists from the Institute of High-Temperature Electrochemistry, Ural Branch of the Russian Academy of Sciences, and the Ural Federal University has obtained a ceramic material for hydrogen energy. Chemists managed to synthesize, study, and improve the properties of layered barium stannate. This material can be used in fuel cells and electrolyzers. They are used to produce hydrogen or electrical energy. The scientists described the synthesis process and chemical properties of the material in an article in the Journal of Alloys and Compounds. 

"We have been investigating barium stannate, an understudied layered material, for use in high-temperature devices. We prepared samples and found that it begins to partially decompose into oxides when stored outdoors for long periods of time. We were able to improve the stability by adding lanthanum, but we did not completely eliminate the problem. However, since the material as a whole has quite good electron-conducting properties, it can certainly be used for applications as long as its contact with air is excluded. For example, lithium-containing components in lithium-ion batteries are also used in isolation because they ignite in contact with air," explains study co-author Dmitry Medvedev, head of the Hydrogen Energy Laboratory at the Ural Federal University.

Disrupted flow of brain fluid may underlie neurodevelopmental disorders

The addition of a magenta tracer molecule illustrates the flow of fluid around the brain, revealing that neurons in the hippocampus (cyan), the brain’s memory center, are awash in fluid. Researchers at Washington University School of Medicine in St. Louis have discovered that this fluid flows to areas critical for normal brain development and function, suggesting that disruptions to its circulation may play an underrecognized role in neurodevelopmental disorders.
Photo Credit: Shelei Pan and Peter Yang/School of Medicine

The brain floats in a sea of fluid that cushions it against injury, supplies it with nutrients and carries away waste. Disruptions to the normal ebb and flow of the fluid have been linked to neurological conditions including Alzheimer’s disease and hydrocephalus, a disorder involving excess fluid around the brain.

Researchers at Washington University School of Medicine in St. Louis created a new technique for tracking circulation patterns of fluid through the brain and discovered, in rodents, that it flows to areas critical for normal brain development and function. Further, the scientists found that circulation appears abnormal in young rats with hydrocephalus, a condition associated with cognitive deficits in children.

The findings, available online in Nature Communications, suggest that the fluid that bathes the brain — known as cerebrospinal fluid — may play an underrecognized role in normal brain development and neurodevelopmental disorders.

Size of insects are shaped by temperature and predators

Many bird species in the tropics catch and eat damselflies and dragonflies. Here is a Rufous-tailed Jacamar that has caught a large dragonfly in the Atlantic Forest of Brazil
Photo Credit: Erik Svensson

The size of dragonflies and damselflies varies around the globe. These insects are generally larger in temperate areas than in the tropics. According to a new study from Lund University in Sweden, this is caused by a combination of temperatures and the prevalence of predators.

In a large global comparative study of this ancient order of insects, researchers have studied how body size varies geographically and between different species. They compared the size of these insects in the hot tropics with the cooler, temperate regions to quantify geographical variation and understand its causes. This was done by analyzing size data and fossil data for various species of dragonflies and damselflies (two suborders of the order Odonata).

“Two hundred million years ago, these insects were larger in the tropics than in temperate climates. That trend has since reversed, however, and the opposite is now true, with larger species generally found at our northerly latitudes. We believe that this is partly caused by the evolutionary appearance of birds” says Erik Svensson, biologist at Lund University.

Inhalable ‘SHIELD’ Protects Lungs Against COVID-19, Flu Viruses

Photo Credit: Robina Weermeijer

Researchers have developed an inhalable powder that could protect lungs and airways from viral invasion by reinforcing the body’s own mucosal layer. The powder, called Spherical Hydrogel Inhalation for Enhanced Lung Defense, or SHIELD, reduced infection in both mouse and non-human primate models over a 24-hour period, and can be taken repeatedly without affecting normal lung function.

“The idea behind this work is simple – viruses have to penetrate the mucus in order to reach and infect the cells, so we’ve created an inhalable bioadhesive that combines with your own mucus to prevent viruses from getting to your lung cells,” says Ke Cheng, corresponding author of the paper describing the work. “Mucus is the body’s natural hydrogel barrier; we are just enhancing that barrier.”

Cheng is the Randall B. Terry, Jr. Distinguished Professor in Regenerative Medicine at North Carolina State University’s College of Veterinary Medicine and a professor in the NC State/UNC-Chapel Hill Joint Department of Biomedical Engineering.

The inhalable powder microparticles are composed of gelatin and poly(acrylic acid) grafted with a non-toxic ester. When introduced to a moist environment – such as the respiratory tract and lungs – the microparticles swell and adhere to the mucosal layer, increasing the “stickiness” of the mucus.

New models shed light on life’s origin

Rochester researcher Dustin Trail used experiments and zircon chemistry to build more accurate computer models of fluids that act as pathways from inner Earth to Earth’s surface. The models allow researchers to simulate what metals—such as manganese (pictured)—may have been transported to Earth’s surface when life first emerged, about four billion years ago. “Our research shows that metals like manganese may function as important links between the ‘solid’ Earth and emerging biological systems at Earth’s surface,” Trail says
Photo Credit: Vanderlei Alves da Silva

The research reveals clues about the physical and chemical characteristics of Earth when life is thought to have emerged.

The first signs of life emerged on Earth in the form of microbes about four billion years ago. While scientists are still determining exactly when and how these microbes appeared, it’s clear that the emergence of life is intricately intertwined with the chemical and physical characteristics of early Earth.

“It is reasonable to suspect that life could have started differently—or not at all—if the early chemical characteristics of our planet were different,” says Dustin Trail, an associate professor of earth and environmental sciences at the University of Rochester.

But what was Earth like billions of years ago, and what characteristics may have helped life to form? In a paper published in Science, Trail and Thomas McCollom, a research associate at the University of Colorado Boulder, reveal key information in the quest to find out. The research has important implications not only for discovering the origins of life but also in the search for life on other planets.

Large-scale genetic analysis shows microRNAs in human pancreas associated with diabetes

 NIH study identifies new molecules involved in diabetes.
Illustration Credit: CFVI

In a new large-scale genetic analysis, scientists have found a set of small RNA molecules, called microRNAs, in human pancreatic cells that are strongly associated with type 2 diabetes. Researchers discovered the microRNAs in groups of cells called pancreatic islets, which produce hormones, such as insulin, that the body uses to regulate energy levels.

In people with diabetes, the islets fail to produce sufficient insulin to control blood sugar, which is why understanding the basic biology of pancreatic islets is important for human health.

The study, led in part by scientists at the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health, will inform future studies on the early detection and treatment of diabetes. The results were published in Proceedings of the National Academy of the Sciences.

Previous research with animal or cell-based models over the past two decades suggests that certain microRNAs, which are involved in controlling which genes are turned on and off in cells, may help pancreatic islets normally develop and function.

Mushrooms magnify memory by boosting nerve growth

Lion's mane mushroom
Photo Credit: Kier... in Sight

Researchers from The University of Queensland have discovered an active compound from an edible mushroom that boosts nerve growth and enhances memory.

Professor Frederic Meunier from the Queensland Brain Institute said the team had identified new active compounds from the mushroom, Hericium erinaceus.

“Extracts from these so-called ‘lion’s mane’ mushrooms have been used in traditional medicine in Asian countries for centuries, but we wanted to scientifically determine their potential effect on brain cells,” Professor Meunier said.

“Pre-clinical testing found the lion’s mane mushroom had a significant impact on the growth of brain cells and improving memory.

“Laboratory tests measured the neurotrophic effects of compounds isolated from Hericium erinaceus on cultured brain cells, and surprisingly we found that the active compounds promote neuron projections, extending and connecting to other neurons.

Harmful Effects of Long-Term Alcohol Use Documented in Blood Protein Snapshot

Jon Jacobs recently found that a particular combination of blood proteins indicates alcohol-associated hepatitis, a deadly liver disease. 
Photo Credit: Eddie Pablo III | Pacific Northwest National Laboratory

Biochemist Jon Jacobs has analyzed the blood of patients with diseases and conditions such as Ebola, cancer, tuberculosis, hepatitis, diabetes, Lyme disease, brain injury and influenza.

But never has he seen blood chemistry gone so awry as when he and colleagues took an in-depth look at the protein activity in the blood of patients with alcohol-associated hepatitis, a severe form of liver disease caused by heavy drinking for many years.

“The proteins in these patients are more dysregulated than in any other blood plasma that we’ve analyzed,” said Jacobs, a scientist at the Department of Energy’s Pacific Northwest National Laboratory. “Almost two-thirds of the proteins we measured are at unusual levels. This is a snapshot of what’s going on in the body of a person with this disease and reflects just how severe a disease this is.”

That “snapshot” is a measurement of proteins that change in patients with the disease. The unique combination of changes in protein activity marks an important step toward development of a simple blood test to diagnose alcohol-associated hepatitis.

Jacobs and colleagues, including scientists and physicians from the Veteran Affairs Long Beach Healthcare System and the University of Pittsburgh, published their findings recently in the American Journal of Pathology. Corresponding authors of the study are Jacobs and Timothy Morgan, a gastroenterologist at VA Long Beach who has treated patients with the disease for more than 35 years.

Can clay capture carbon dioxide?

Sandia National Laboratories bioengineer Susan Rempe, left, and chemical engineer Tuan Ho peer through an artistic representation of the chemical structure of a kind of clay. Their team is studying how clay could be used to capture carbon dioxide.
Photo Credit: Craig Fritz

The atmospheric level of carbon dioxide — a gas that is great at trapping heat, contributing to climate change — is almost double what it was prior to the Industrial Revolution, yet it only constitutes 0.0415% of the air we breathe.

This presents a challenge to researchers attempting to design artificial trees or other methods of capturing carbon dioxide directly from the air. That challenge is one a Sandia National Laboratories-led team of scientists is attempting to solve.

Led by Sandia chemical engineer Tuan Ho, the team has been using powerful computer models combined with laboratory experiments to study how a kind of clay can soak up carbon dioxide and store it.

The scientists shared their initial findings in a paper published earlier this week in The Journal of Physical Chemistry Letters.

“These fundamental findings have potential for direct-air capture; that is what we’re working toward,” said Ho, lead author on the paper. “Clay is really inexpensive and abundant in nature. That should allow us to reduce the cost of direct-air carbon capture significantly, if this high-risk, high-reward project ultimately leads to a technology.”

Scientists boost quantum signals while reducing noise

This superconducting parametric amplifier can achieve quantum squeezing over much broader bandwidths than other designs, which could lead to faster and more accurate quantum measurements.
 Image Credit: Courtesy of the researchers

A certain amount of noise is inherent in any quantum system. For instance, when researchers want to read information from a quantum computer, which harnesses quantum mechanical phenomena to solve certain problems too complex for classical computers, the same quantum mechanics also imparts a minimum level of unavoidable error that limits the accuracy of the measurements.

Scientists can effectively get around this limitation by using “parametric” amplification to “squeeze” the noise –– a quantum phenomenon that decreases the noise affecting one variable while increasing the noise that affects its conjugate partner. While the total amount of noise remains the same, it is effectively redistributed. Researchers can then make more accurate measurements by looking only at the lower-noise variable.

A team of researchers from MIT and elsewhere has now developed a new superconducting parametric amplifier that operates with the gain of previous narrowband squeezers while achieving quantum squeezing over much larger bandwidths. Their work is the first to demonstrate squeezing over a broad frequency bandwidth of up to 1.75 gigahertz while maintaining a high degree of squeezing (selective noise reduction). In comparison, previous microwave parametric amplifiers generally achieved bandwidths of only 100 megahertz or less.